Leukotriene B4 (LTB4) is one kind of arachidonic acid metabolites and one of the most potent activation substances of neutrophil and macrophage (see e.g., Samuelsson et al., “science”, (US), (1987), vol. 237, p. 1171-1176 and Shimizu et al., “Journal of Neurochemistory”, (UK), (1990), vol. 55, p. 1-15). It is known that action of LTB4 on neutrophil or macrophage results in the induction of various responses important for biological defense, such as adhesion to vascular endothelial cells, degranulation of lysosome enzymes, production of active oxygen, chemotaxis into inflammatory tissues and the like. However, overproduction of LTB4 is deeply involved in the formation and aggravation of various diseases accompanied by inflammations or allergic responses, psoriasis (see e.g., Iversen et al., “Skin Pharmacology”, (US), (1997), vol. 10, p. 169-177), bronchial asthma (see e.g., Turner et al., “The Journal of Clinical Investigation”, (US), (1996), vol. 97, p. 381-387), rheumatoid arthritis (see e.g., Griffiths et al., “Proceedings of the National Academy of Science of the USA”, (US), (1995), vol. 92, p. 517-521), inflammatory bowel disease (see e.g., Sharon et al., “Gastroenterology”, (US), (1984), vol. 86, p. 453-460), ischemic renal failure (see e.g., Noiri et al., “Proceedings of the National Academy of Science of the USA”, (US), (2000), vol. 97, 823-828) and the like. Therefore, the development of a therapeutic agent capable of selectively inhibiting the production or action of LTB4 in various ways has been desired for the prophylaxis or treatment of these diseases. In recent years, it has been clarified that LTB4 receptors include two kinds of receptors (BLT1, BLT2) having different expression distributions and affinities (see e.g., Yokomizo et al., “Nature”, (UK), (1997), vol. 387, p. 620-624 and Yokomizo et al., “The Journal of the Experimental Medicine”, (2000), vol. 192, p. 421-431). Therefore, broadening of the range of selection of LTB4 inhibitor has been desired more than ever.
On the other hand, while benzofuran derivatives having a leukotriene inhibitory action have been disclosed (e.g., JP-A-61-17579, JP-A-5-202040, JP-A-5-317024 etc.), the selectivity to LTB4 has not been disclosed.
An object of the present invention is to increase diversity of and broaden the selection range of leukotriene inhibitors, BLT2 competitive inhibitors, agents for the prophylaxis or treatment of allergy, agents for the prophylaxis or treatment of asthma and agents for the prophylaxis or treatment of inflammation, by providing novel compounds having a potent leukotriene (particularly leukotriene B4) inhibitory action and a BLT2 competitive inhibitory action as well as high safety.